Aging impairs the neurovascular interface in the heart-Reference-Cited by-同舟云学术

Aging impairs the neurovascular interface in the heart

Published:2023-08-25 Issue:6660 Volume:381 Page:897-906
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Wagner Julian U. G.¹²³^ORCID,Tombor Lukas S.¹²³^ORCID,Malacarne Pedro Felipe⁴,Kettenhausen Lisa-Maria¹,Panthel Josefine¹,Kujundzic Haris¹,Manickam Nivethitha¹³,Schmitz Katja¹,Cipca Maria¹^ORCID,Stilz Kathrin A.¹^ORCID,Fischer Ariane¹^ORCID,Muhly-Reinholz Marion¹,Abplanalp Wesley T.¹²³^ORCID,John David¹^ORCID,Mohanta Sarajo K.⁵⁶⁷^ORCID,Weber Christian⁵⁶⁷⁸^ORCID,Habenicht Andreas J. R.⁵⁶⁷^ORCID,Buchmann Giulia K.⁴^ORCID,Angendohr Stephan⁹^ORCID,Amin Ehsan¹⁰^ORCID,Scherschel Katharina¹⁰¹¹¹²^ORCID,Klöcker Nikolaj¹⁰,Kelm Malte⁹¹²^ORCID,Schüttler Dominik⁷¹³¹⁴¹⁵^ORCID,Clauss Sebastian⁷¹³¹⁴¹⁵^ORCID,Günther Stefan³¹⁶^ORCID,Boettger Thomas²³¹⁶^ORCID,Braun Thomas²³¹⁶^ORCID,Bär Christian¹⁷¹⁸,Pham Minh-Duc¹⁹²⁰^ORCID,Krishnan Jaya¹³¹⁹^ORCID,Hille Susanne²¹²²^ORCID,Müller Oliver J.²¹²²^ORCID,Bozoglu Tarik⁷²³^ORCID,Kupatt Christian⁷²³^ORCID,Nardini Eleonora²⁴^ORCID,Osmanagic-Myers Selma²⁴^ORCID,Meyer Christian¹¹¹²^ORCID,Zeiher Andreas M.²³^ORCID,Brandes Ralf P.²³⁴^ORCID,Luxán Guillermo¹²³^ORCID,Dimmeler Stefanie¹²³^ORCID

Affiliation:

1. Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.

2. German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main, 60590 Frankfurt, Germany.

3. Cardiopulmonary Institute (CPI), 60590 Frankfurt, Germany.

4. Institute for Cardiovascular Physiology, Goethe University Frankfurt, 60590 Frankfurt, Germany.

5. Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München (LMU), 80336 Munich, Germany.

6. Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.

7. German Center for Cardiovascular Research (DZHK), Partner Site Munich, Munich Heart Alliance (MHA), 80802 Munich, Germany.

8. Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.

9. Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.

10. Institute of Neural and Sensory Physiology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.

11. Division of Cardiology/Angiology/Intensive Care, EVK Düsseldorf, cNEP, cardiac Neuro- and Electrophysiology Research Consortium, 40217 Düsseldorf, Germany.

12. Cardiovascular Research Institute Düsseldorf (CARID), Medical Faculty and University Hospital of Düsseldorf, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.

13. Department of Medicine I, University Hospital Munich, Ludwig Maximilian University, 81377 Munich, Germany.

14. Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, 81377 Munich, Germany.

15. Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICON), LMU Munich, 80539 Munich, Germany.

16. Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.

17. Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany.

18. REBIRTH-Centre for Translational Regenerative Medicine, Hannover Medical School, 30625 Hannover, Germany.

19. Department of Medicine, Cardiology, Goethe University Hospital, 60590 Frankfurt, Germany.

20. Genome Biologics, 60590 Frankfurt am Main, Germany.

21. Department of Internal Medicine III, University Hospital Schleswig-Holstein, University of Kiel, 24105 Kiel, Germany.

22. German Centre for Cardiovascular Research (partner site Hamburg/Kiel/Lübeck), 24105 Kiel, Germany.

23. Klinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University of Munich, 81675 Munich, Germany.

24. Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, A-1090 Vienna, Austria.

Abstract

Aging is a major risk factor for impaired cardiovascular health. Because the aging myocardium is characterized by microcirculatory dysfunction, and because nerves align with vessels, we assessed the impact of aging on the cardiac neurovascular interface. We report that aging reduces nerve density in the ventricle and dysregulates vascular-derived neuroregulatory genes. Aging down-regulates microRNA 145 (miR-145) and derepresses the neurorepulsive factor semaphorin-3A. miR-145 deletion, which increased Sema3a expression or endothelial Sema3a overexpression, reduced axon density, mimicking the aged-heart phenotype. Removal of senescent cells, which accumulated with chronological age in parallel to the decline in nerve density, rescued age-induced denervation, reversed Sema3a expression, preserved heart rate patterns, and reduced electrical instability. These data suggest that senescence-mediated regulation of nerve density contributes to age-associated cardiac dysfunction.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.ade4961

Reference43 articles.

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